Falls and fall-related injuries are an all too common occurrences in the prehospital environment and are especially prevalent within the older population. The National Institute for Health and Care Excellence (NICE) (2013) estimates that 30% of those aged >65 years and half of those aged >80 years experience at least one fall per year. NICE also states that falls cost the NHS more than £2.3 billion annually and greatly affect the mortality of those who experience them.
The article aims to reiterate and extend on an overview of rhabdomyolysis for prehospital clinicians written by Nellist and Lethbridge (2013), with an greater focus on falls in elderly people, given that this is a life-threatening but lesser-known complication of falls in this population (Criner et al, 2002).
This paper will then examine the underlying pathophysiology of rhabdomyolysis and the risk factors that may increase the likelihood of it developing in older people who have fallen. Suggestions will be made regarding identifying the potential for its development and therefore facilitating its early recognition and treatment to reduce harm caused. Recommendations are made to increase awareness and recognition of the condition.
What is rhabdomyolysis?
Rhabdomyolysis was first reported in German literature in 1881; however, the symptoms and clinical presentation were first described during the blitz of London. Bywaters (1941) noted four cases of a similar presentation in casualties of the aftermath of a bombing raid, all of whom had experienced crush injuries. All four patients initially presented with crushed limbs after prolonged periods of being trapped, and all four died within the following week after their conditions gradually had appeared to improve before a rapid deterioration occurred, leading to death. Necropsy in all four revealed degenerative changes in the kidneys.
Rhabdomyolysis is well recognised in modern medicine (Khan, 2009; Adams and Arbogast, 2013; Parekh, 2017). While there are no data on prevalence in the UK, at least 26 000 people are thought to develop the condition annually in the United States (Harriston, 2004). The condition has been dubbed the ‘hidden killer’ (Criner et al, 2002).
Rhabdomyolysis is described in Rosen's Emergency Medicine as:
‘a potentially life-threatening condition characterized by the breakdown of skeletal muscle and the release into the circulatory system of intracellular contents’.
Adams and Arbogast (2013) state that rhabdomyolysis is characterised by skeletal muscle injury that alters the integrity of the cell membrane, for which there are numerous causes.
Simply speaking, this condition is caused by the breakdown of muscle, often causing death to the muscle cell and the release of its contents into the circulation via the bloodstream. The products released include potassium, myoglobin, creatine kinase (CK) and lactate hydrogenase alongside others (Huerta-Alardín et al, 2005).
The underlying pathology of rhabdomyolysis most commonly involves: direct damage to the sarcolemma, such as a mechanical or toxic insult to the muscle cell (Verma, 2006); and/or depletion of adenosine triphosphate within the myocyte (Adams and Arboghast, 2013). This leads to muscle damage within 2 hours, irreversible anatomic and functional changes within 4 hours, and muscle necrosis in as little as 6 hours (Parekh, 2017). This can occur during periods of immobilisation, where prolonged compression of the muscle causes cell ischaemia, leading to myocyte necrosis and the release of cell products into the bloodstream (Huerta-Alardín et al, 2005).
Diagnosis and clinical presentation
Adams and Arbogast (2013) suggest a definition of clinical rhabdomyolysis as:
‘that of an absolute CK level of greater than 15 000 units/litre (U/L), or a CK level of greater than 5000 U/L and any of the following: crush injury; AKI (acute kidney injury); myoglobinuria; acidosis, disseminated intravascular coagulation, hypocalcaemia or hyperkalaemia; massive muscle injury; or prolonged extrication/initial evacuation delayed longer than four hours.’
A wide range of signs and symptoms occur in patients with rhabdomyolysis, although these are often subtle and non-specific (Huerta-Alardín et al, 2004). Symptoms include generalised malaise and myalgia, dysuria, fever and vomiting alongside the classic triad of symptoms: muscle pain, weakness and dark, tea-coloured urine (Parekh, 2017). However, up to 50% of patients do not complain of muscular symptoms at all (Parekh, 2017) and the classic triad of symptoms occur in fewer than 10% of those diagnosed (Huerta-Alardín et al, 2004).
As there are a variety of generic symptoms, patients often present under the guise of another medical condition. For instance, muscle tenderness with pectoral involvement may be interpreted as cardiac pain; back pain may mimic renal colic; and calf pain may result in medical investigation for deep vein thrombosis (Huerta-Alardín et al, 2004).
The first indication of rhabdomyolysis may be the presentation of dysuria and dark-coloured urine. On discovering this, prehospital clinicians would be forgiven for suspecting a urinary tract infection. A study by Bent et al (2002) found that 50% of women with a singular urinary tract infection symptom (dysuria, haematuria, altered frequency or back pain) were likely to be diagnosed with an infection. This number rose to 90% when exhibiting specific combinations of symptoms—such as dysuria and increased frequency without vaginal discharge or irritation—even without urinalysis (Bent et al, 2002).
As many patients with rhabdomyolysis do not exhibit symptoms at all (Adams and Arbogast, 2013; Parekh, 2017), this condition cannot be excluded just according to the lack or presence of symptoms. The only definitive means of testing for rhabdomyolysis are via blood tests measuring CK levels (Adams and Arbogast, 2013), a procedure many ambulance paramedics do not perform.
Therefore, more emphasis should be placed on accurate history taking with a high index of suspicion when assessing a patient's potential risk of developing the condition (Keltz et al, 2013).
Causes and risk factors
Rhabdomyolysis has many causes (Tables 1 and 2). These range from direct muscle and ischaemic injury to toxins and drug use (including illicit substances, prescription and over-the-counter medications, overexertion during exercise and various infections and medical conditions (Adams and Arbogast, 2013). Essentially, they are anything that results in the breakdown of the muscle to a significant enough level to release the waste products into the bloodstream.
| Trauma and compression | Vessel occlusion | ||
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| Excessive muscle activity | |||
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| Tetanus | Sepsis | ||
| Electrical current | Hyperthermia | ||
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| Non-physical causes | |||
| Metabolic syndromes | Electrolye imbalances | ||
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| Infections | Drugs interactions (Table 2) | ||
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Toxins | |
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| Endocrine disorders | Autuimmune disorders | ||
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| Antidepressants and antipsychotics | |
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| Sedative hypnotics | |
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| Antihistamines | |
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| Antilipemic agents | |
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| Drugs of addiction | |
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| Other drugs | |
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While traumatic rhabdomyolysis usually occurs as result of a traumatic injury, such as a road traffic collision, building collapse or crush injuries, muscle compression often presents in people who have been confined to the same position for prolonged periods of time.
Three patient circumstances found to result in rhabdomyolysis, documented by Adams and Arbogast (2013), were: having undergone prolonged surgical interventions with improper positioning (high lithotomy or lateral decubitus position); having undergone long-term confinement; and being in a coma. Furthermore, a study of 97 patients by Fernandez et al (2005) found immobilisation to be the third most common cause of rhabdomyolysis after cocaine use and excessive exercise. This study found that, despite most patients being aged <55 years, rhabdomyolysis was still prevalent.
In the United States, in a recent epidemiological study of rhabdomyolysis in older people, Wongrakpanich et al (2018) found in 167 patients, that ‘falls; with or without immobilisation’ was the most frequent cause at 56%. This is significant, since the next two most frequent causes of rhabdomyolysis were ‘unknown etiology’ and ‘seizures’, accounting for just 12% and 5.4% respectively. The incidence of acute kidney injury (AKI) was found to be 69%. Patients with AKI were more likely to die than those without during the same admission (13% versus 2%) (Wongrakpanich et al, 2018).
Alongside prolonged immobilisation, another common cause of rhabdomyolysis is statin use (Antons et al, 2006). In the UK, statins are widely prescribed, with O'Keeffe et al (2016) finding that 45–50% of people aged 70–84 years were being prescribed a statin of some kind. During a study looking at the association between statin-associated myopathy and skeletal muscle damage, Mohaupt et al (2009) found that 50% of patients exhibited muscle damage on biopsy which was associated with statin use, even when taking low doses.
Increased age has also been found to be a risk factor. In a descriptive retrospective study of 449 Spanish patients with rhabdomyolysis, Herráez García et al (2012) found that, while there was no significant association between CK levels and mortality, there was a strong association between age and mortality. The main cause of rhabdomyolysis in these patients was trauma, followed by sepsis and immobility, and with 90% of total deaths occurring in patients aged >60 years. Baeza-Trinidad et al (2015) found similar results, showing that although initial CK levels were not indicative or mortality, older people with rhabdomyolysis had a greater association with AKI and mortality.
Nellist and Lethbridge (2013) provide a good summary of rhabdomyolysis for prehospital clinicians. However there is only a brief mention of statins as an exogenous cause, although these are an important factor. Rhabdomyolysis can occur solely from statin use (Mohaupt et al, 2009; Antons et al, 2006). This, alongside prolonged periods of immobilisation, frailty and older age being documented as exacerbating factors (Herráez García et al, 2012; Baeza-Trinidad et al, 2015), puts elderly fallers at a significant risk of developing this ‘hidden killer’ of a condition (Criner et al, 2002).
Complications of rhabdomyolysis
One of the most serious complications of rhabdomyolysis is AKI (Bosch et al, 2009). While literature varies regarding the percentage of patients with rhabdomyolysis who develop AKI, Grossman et al (1974) suggested in an important older study that rhabdomyolysis (from all causes) accounted for 5–25% of all cases of AKI. Lima et al (2008) reported that AKI occurs in 33–50% of people diagnosed with rhabdomyolysis, with a recent clinical study suggesting that patients developing AKI have mortality rates in a range of 7–80% (Kasaoka et al, 2010). AKI is the most common cause of organ dysfunction in critically ill adults, with an incidence of 34% and an observed in-hospital mortality as high as 62% (Doyle and Forni, 2016).
One of the most significant products released during muscle injury is myoglobin. Myoglobin is similar in function to haemoglobin; it is responsible for oxygen storage but within muscle tissue as opposed to in the bloodstream. Myoglobin allows oxygen delivery to muscle cells during periods of reduced oxygen supply to the muscle tissue: increased levels of myoglobin are often found in marine animals that undergo extended periods of apnoea when diving and in humans living in areas of high altitude (Ordway and Garry, 2004).
Once in the bloodstream, myoglobin is filtered through the glomerulus. As water is reabsorbed in the renal tubules, the concentration of myoglobin rises until it causes an obstructive cast. This obstructive cast causes acute tubular necrosis, resulting in AKI (Ordway and Garry, 2004; Rosen and Stillman, 2008).
Hyperkalaemia is the most serious electrolyte imbalance observed in rhabdomyolysis, occurring in 10–40% of patients (Adams and Arbogast, 2013). Ninety-eight per cent of the body's potassium is found in intracellular spaces, and necrosis of as little as 100 g of muscle is predicted to increase the serum potassium levels by 1.0 mmol (Parekh, 2017). For reference, normal serum potassium levels are between 3.5 mmol and 5.0 mmol (Wians, 2022), with hyperkalaemia being diagnosed when potassium levels exceed this. The effects of hyperkalaemia can be severe, with the most serious being cardiac manifestations such as cardiac arrest resulting from ventricular fibrillation or asystole (Buttner and Burns, 2022).
Elderly fallers and the ambulance service
Fifty per cent of the population aged over 80 years are likely to fall at least once a year (NICE, 2013). In the UK, ambulance services triage emergency calls between four categories. Category 1 and category 2 calls are designated as life threatening, with response targets of 7 minutes and 18 minutes respectively (NHS England, 2017a). Most elderly patients who have fallen and report no injury will be triaged as a category 3 (C3), with a response target of 120 minutes (NHS England, 2017a). In December 2017, an ambulance arrived at C3 incidents in a mean time of 78 minutes, with a 90th centile of 186 minutes. The longest response recorded was a 90th centile of 317 minutes (5 hours 17 minutes) (NHS England, 2017b).
In 2003, 8% of the total workload the London Ambulance Service (LAS) attended was regarding patients aged ≥65 years who had fallen. Forty per cent of these were discharged on scene by ambulance crews (Snooks et al, 2006). Of 175 patients included in a retrospective study, 47% made further contact with the LAS in the following 2-week period, with just under half of those making two or more 999 calls. The 2-week mortality rate in the study group was found to be 2.3%, significantly higher than that of the general population of the same age in London at 0.43% (Snooks et al, 2006). While this study by Snooks et al (2006) is now outdated, its seminal nature is still worthy of note.
Increased ambulance reattendance by patients left at home following a fall has also been documented in the United States, with Cone et al (2012) reporting a reattendance rate of 52% at 30 days, with half of those requiring admission to hospital on the later attendance because of ‘medical’ reasons. In New South Wales, Simpson (2014) found non-transported falls patients had a higher rate of death (3.3% versus 1.7%) and ambulance reattendance (15.6% versus 9.4%) at 28 days than those conveyed to hospital, with a 2.7 greater risk of death in the first 5 days following the first ambulance attendance. Simpson (2014) also reports than 10% of older fallers receiving an ambulance response experience a long lie of 1 hour or more.
In a follow-up study by Snooks et al (2017), LAS paramedics were given a clinical protocol with a referral pathway to enable them to better assess and treat elderly people who had fallen. Among other factors, part of this protocol advised that any patient who had experienced a ‘long lie’ of 2 hours or greater needed to attend at the emergency department. However, no difference was found in conveyance rates or mortality after attendance when compared to the control group. A smaller proportion of patients in the intervention group made further emergency calls at 1 month (19% versus 22%) and fewer patients in this group were left at home without referral of any kind (23% versus 30%) (Snooks et al, 2017).
Prehospital management and treatment
The treatment of rhabdomyolysis mainly revolves around preserving renal function to reduce the risk of AKI; the longer it takes for rehydration treatment to be started, the more likely it is that AKI will develop (Chatzizisis et al, 2008; Torres et al, 2015). If fluid therapy is started before myoglobin is filtered into the renal tubules, renal blood flow, estimated glomerular filtration rate and urination are increased. This helps prevent myoglobinuric obstructive casts from forming, reducing the risk of AKI developing (Chatzizisis et al, 2008). Adams and Arbogast (2013) state that the two most common contributors to the development of AKI are slow and inadequate fluid resuscitation.
In-hospital treatment comprises aggressive fluid resuscitation, alkalinisation therapy, diuretics and, if required, dialysis (Parekh, 2017). The only treatment available to paramedics when suspecting rhabdomyolysis is fluid resuscitation, which is recommended by Keltz et al (2014). In traumatic rhabdomyolysis, it is recommended to secure a large intravenous cannula as soon as possible and start a normal saline infusion immediately to reduce the risk of AKI developing (Gunal et al, 2004; Khan, 2009).
While there is a large amount of literature recommending early fluid therapy in suspected rhabdomyolysis (Chatzizisis et al, 2008; Adams and Arbogast, 2013; Torres et al, 2015), there are no specific guidelines for paramedics. However, sodium chloride infusion is not contraindicated for paramedics who suspect rhabdomyolysis, with UK ambulance guidelines simply indicating fluid therapy for ‘general medical conditions without haemorrhage’ (Brown et al, 2016).
Because of the risk of hyperkalaemia, monitoring via electrocardiogram is also recommended, as hyperkalaemia may produce abnormalities such as peaked T-waves, absent P-waves and widening of the QRS complex (Slovis and Jenkins, 2002). The only drug used in treating hyperkalaemia that paramedics carry is salbutamol, which has been shown to be effective at shifting potassium from the extracellular to the intracellular compartment. However, this is not recommended without first using a medication, such as calcium gluconate, to stabilise the myocardium (Nyirenda et al, 2009). Paramedics do not carry such drugs as standard.
In context of the prehospital management by paramedics, emphasis should not be placed on treatment of the condition once established but on prevention. By recognising those at risk of developing this condition, such as those with long lies, who are frail or who have multiple comorbidities, referral or transport to an emergency department for blood tests can prevent a fatal complication from occurring.
Conclusion
There is very little data relating to rhabdomyolysis in the elderly, with potentially the first epidemiological study being published in 2018 (Wongrakpanich et al, 2018). However, the literature reviewed shows several factors are clear.
First, elderly fallers make up a large percentage of the total workload of the ambulance service, with a large number of patients being left at home. Of those non-transported patients, rates of ambulance reattendance, hospital admission and mortality are significantly higher than in those conveyed to hospital.
Second, there is a strong correlation between prolonged immobilisation and developing rhabdomyolysis. The risk is greater in those taking statins, with a large incidence of rhabdomyolysis developing in those simply taking statins. Fifty per cent of the population aged >80 years are likely to fall at least once a year and 45–50% of those in this age range are prescribed a statin.
Finally, there is a well-established relationship between rhabdomyolysis and the development of AKI. Some 33–50% of those diagnosed with rhabdomyolysis go on to develop AKI. While early rehydration treatment helps prevent AKI, those who go untreated face a dangerous complication that has an in-hospital mortality rate of 62%.
LEARNING OUTCOMES
After completing this module, the paramedic will be able to:
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